RESUMO
A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10-7, 4.3 × 10-9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.
RESUMO
A 78 year-old male was admitted for rehabilitation after a trans-tibial amputation three months earlier. Scheduled training with a prosthetic leg was postponed due to muscle atrophy and weakness. As the patient's status deteriorated, blood results showed worsening hyponatremia.Work-up revealed pituitary insufficiency caused by a pituitary mass. The patient's general health improved greatly and the hyponatremia corrected after hormonal replacement therapy with hydrocortisone, thyroxin and testosterone was initiated. Key words: hyponatremia, malaise, weight loss, pituitary insufficiency, pituitary adenoma.